Summary of Work: The Neuro-otology Branch has focused its activities on two major areas of inner ear biology and medicine. Individuals affected by von Hippel Lindau disease (VHL) are predisposed to hearing and balance impairment due to primary adenocarcinomas of the endolymphatic sac of the inner ear. A collaborative IRB approved protocol to investigate hearing and balance function and preservation by surgery is underway. Study of these individuals, in collaboration with the urologic oncology branch of the NCI and the surgical neurology branch of the NINDS, has provided a unique pathologic model of inner ear biology. Molecular genetic studies are underway to define whether certain mutations of the VHL gene result in these rare tumors. Audiologic and clinical neurotologic evaluations are being conducted to define the natural history of hearing loss, balance dysfunction and tinnitus associated with the tumors. These investigations can provide better understanding of inner ear biology and may serve as a model for inner ear diseases such as Meniere's disease. Future efforts may include organ specific VHL knock-out models as well as the potential ligands and receptors involved in the VHL pathway of the inner ear. Collaborative efforts with the NIAID have been directed at characterizing the neuro-otologic and audiologic features of individuals affected by chronic neuroborreliosis. In a manner analagous to that seen in syphilitic central nervous system disease, chronic infection of the central nervous system by the lyme pathogen, Borrelia burgdorferi, has been implicated in the pathogenesis of sensorineural hearing loss, vertigo or other vestibular disturbances, as well as tinnitus in individuals with Lyme disease. The incidence of specific audiovestibular symptoms, the characterization of central vs. peripheral auditory system abnormalities, and the effects of antimicrobial therapy on these parameters are being examined by the NIDCD Neuro-otology Branch.